Low plasma levels of FGF-2 and PDGF-BB are associated with cardiovascular events in type II diabetes mellitus (diabetes heart study)

Objective: We tested associations of the growth factors VEGF, FGF-2, HGF and PDGF-BB with coronary artery calcium scores and cardiovascular events (CVD) in type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study selected 40 frequency matched (by age, gender and race) subjects with T2DM from the first (0–111) and the third (> 1400) coronary artery calcium (CAC) score tertiles in the Diabetes Heart Study (DHS), in which 36 were with and 41 were without history of CVD events. Plasma levels of VEGF, FGF-2, HGF and PDGF-BB were measured in all subjects. Results: None of the growth factors was significantly different between the first and third CAC score tertiles. Mean plasma FGF-2 and PDGF-BB levels were significantly higher in the group without prior CVD events compared with the group with prior CVD events [mean(95%CI): 219.20 (194.42–247.15) vs. 152.93 (135.64–172.43) pg/ml, p = 0.03] and [mean(95%CI): 106.70 (89.12–127.74) vs. 61.56 (50.91–74.44) pg/ml, p = 0.03], respectively. Subgroup analysis in the first CAC tertile showed a significantly higher PDGF-BB levels in those without compared with those with CVD events [mean (95%CI): 208.36 (190.57–228.15) vs. 102.93 (80.64–125.21) pg/ml, p = 0.004]. Conclusion: Plasma growth factor levels were not significantly different between the extremes of CAC scores in T2DM. However, low plasma levels of PDGF-BB and FGF-2 are associated with prior cardiovascular events in T2DM. Studies are needed to confirm our results and also to establish temporality of this association.     

Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer

An understanding of the pathology of cervical cancer (CC) mediated by E6/E7 oncoproteins of high-risk human papillomavirus (HPV) was developed by late 80's. But if we look at the present scenario, not a single drug could be developed to inhibit these oncoproteins and in turn, be used specifically for the treatment of CC. The readers are advised not to presume the “viability of E6 protein” as mentioned in the title relates to just druggability of E6. The viability aspect will cover almost everything a researcher should know to develop E6 inhibitors until the preclinical stage. Herein, we have analysed the achievements and shortcomings of the scientific community in the last four decades in targeting HPV E6 against CC. Role of all HPV proteins has been briefly described for better perspective with a little detailed discussion of the role of E6. We have reviewed the articles from 1985 onward, reporting in vitro inhibition of E6. Recently, many computational studies have reported potent E6 inhibitors and these have also been reviewed. Subsequently, a critical analysis has been reported to cover the in vitro assay protocols and in vivo models to develop E6 inhibitors. A paragraph has been devoted to the role of public policy to fight CC employing vaccines and whether the vaccine against HPV has quenched the zeal to develop drugs against it. The review concludes with the challenges and the way forward.     

Clear cell sarcoma of the kidney: report of a case with mandibular metastasis simulating a benign myxomatous tumor

The clear cell sarcoma of the kidney (CCSK) is one of the histologically unfavorable types of childhood renal tumors that has a propensity for osseous metastasis. We have presented the clinical and pathologic findings of the first well-documented case of a CCSK with mandibular metastasis, which was recognized approximately 18 months after the original diagnosis. Microscopically, the mandibular lesion had the features of a benign myxomatous neoplasm with the exception of occasional atypical spindle cells. Electron microscopic observation confirmed the undifferentiated nature of the neoplastic cells. It was concluded that the intensive chemotherapy that was administered to our patient very likely affected the histologic appearance of the mandibular metastasis as well as other recurrent lesions in the abdomen. Our review of the literature revealed only five previous examples of Wilms' tumor that had metastasized to the mandible. At least one of these earlier cases also represented a CCSK.     

Ipsilateral keratoconus associated with long-standing primary hydatid cyst of the orbit

Hydatid cyst is a cyclozoonotic infection of the larvae form of a platyhelminthes Echinococcus granulosus. The majority of hydatid cysts appear in the liver (65%) and lungs (25%). Kidneys and brain are other less common sites for this disease. Only 1% to 2% cases are seen in the maxillofacial region. These commonly appear as cystic lesions located in the mandible, maxillary sinus, orbit, infratemporal fossa, pterygopalatine fossa, parapharyngeal space, tongue, and parotid and submandibular salivary gland. Hydatid cysts of the orbit are rare and account for 1% of all hydatid cysts. The article presents hydatid cyst of the orbit in a 10-year-old child. Clinical features, investigations, surgical approaches, and adjuvant medical management have been emphasized. We believe that the lateral orbital route allows excellent exposure and safe removal of an intraorbital hydatid cyst located posteriorly, superiorly, and laterally without damaging the surrounding important orbital structures. Upper blepharoplasty incision results in good cosmetic outcome.     

Rapid platelet inhibition after a single capsule of Aggrenox®: Challenging a conventional full‐dose aspirin antiplatelet advantage?

Aggrenox is a novel combination of 25 mg of aspirin with 200 mg of sustained release dipyridamole. In a recent large trial (ESPS-2), Aggrenox was twice as effective for secondary stroke prevention as either aspirin or dipyridamole alone, suggesting superior platelet inhibition for combination therapy. We sought to compare the time course of platelet inhibition with Aggrenox compared with escalating doses of non-enteric coated aspirin. Data from 10 healthy volunteers were analyzed. Fasting subjects sequentially ingested aspirin in the following order: 325 mg, 81 mg, 25 mg, and then one pill of Aggrenox after a 3-week interval for aspirin washout. Platelet function was assessed at baseline, 15, 30, 60, and 120 min post-medication with 5 microM epinephrine and 5 microM ADP using conventional aggregometry. Aspirin provided significant (P < 0.01) reduction of platelet aggregation at 15 min post 325 mg, 30 min post 81 mg, and unexpectedly within 60 min after taking 25 mg of aspirin. A single pill of Aggrenox also inhibited platelet aggregation within 1 hr after administration. Aspirin inhibits platelets remarkably fast. Both Aggrenox and a matching dose of aspirin (25 mg) exhibit significant antiplatelet properties within 60 min after ingestion. These findings could be relevant for the optimal balance between the reduction of vascular events via sufficient and rapid platelet inhibition and low risk of bleeding complications associated with the Aggrenox therapy.     

Antileishmanial efficacy of fluconazole and miltefosine in combination with an immunomodulator—picroliv

The chemotherapy of visceral leishmaniasis (VL) has several limitations including resistance and toxicity of the existing drugs. Downregulation of immune system further aggravates the problems. To combat this situation, leishmanicidal efficacy of already marketed standard antifungal drug, fluconazole under the approach of “therapeutic switching” in combination with standard antileishmanial drug, miltefosine, and a potent immunomodulator agent, picroliv, were evaluated in hamsters infected with Leishmania donovani. Animals treated with fluconazole (50 mg/kg × 5 days, oral (p.o.)) + miltefosine (5 mg/kg × 5 days, p.o.) showed enhancement in antileishmanial efficacy (77%), reactive nitrogen species, reactive oxygen species, hydrogen peroxide, and phagocytosis index as compared to those treated with individual drugs. Addition of picroliv to this combination further increased the antileishmanial efficacy from 77% to 88%. Upregulation of cell-mediated immunity was also observed in animals of this group which strengthens the immunomodulatory role of picroliv. These findings suggest a new option for antileishmanial chemotherapy at lower cost and toxicity.     

The Impact of Intimate Partner Violence Exposure in Adolescence and Emerging Adulthood: A Developmental Psychopathology Approach

Despite increased attention on parental intimate partner violence (IPV) exposure, a relative paucity of research has examined the developmental consequences of this traumatic experience within a life span approach. The aim of the present study was to examine how parental IPV exposure may relate to mental health during the transition from adolescence to emerging adulthood. Furthermore, we examined whether the impact of parental IPV exposure was unique from more commonly studied maltreatment experiences, specifically neglect and physical abuse. A large, racially and ethnically diverse sample (N_baseline = 1,042; 56% female; M_age = 15.1, SD = 0.79; 31.4% Hispanic, 29.4% White, 27.9% African American, 3.6% Asian, 7.7% biracial or other) of adolescents completed a baseline assessment for parental physical IPV exposure and maltreatment as well as measures for symptoms of depression, posttraumatic stress, and substance use, annually for 6 consecutive years. Mixed-level modeling was used to examine how parental IPV exposure was uniquely associated with different patterns of mental health across developmental epochs. Findings demonstrated a multifaceted relation with mental health. For internalizing symptoms, the effect was pronounced during adolescence, and neglect increased the risk for depression symptomatology. Meanwhile, parental-IPV-exposed adolescents were at increasing risk for substance use as they aged into adulthood. Symptom levels and trajectories were independent and distinct from maltreatment experiences. This study helps illuminate parental IPV exposure’s unique influence on well-being during vulnerable developmental periods. It also calls attention to the importance of developing suitable intervention/prevention programs to target this vulnerable population.